Recent findings of endothelial progenitor cell activity in the bone marrow and peripheral blood has generated considerable interest in the role of these cells in maintaining and repairing blood vessels. The identity of these cells and the full potential of their functional activity are not well understood. Studies from our laboratory demonstrate that a single cell from a highly purified population of adult hematopoietic stem cells (HSC) can differentiate into endothelial cells and blood cells. We hypothesize that the existence of an HSC derived endothelial progenitor cell population in normal bone marrow. The identification and functional characterization of these bone marrow derived cells is necessary to further understand their contribution to the maintenance of the vascular endothelium. The objective of this proposal is to evaluate the functional potential of bone marrow derived endothelial precursor cell populations in the bone marrow, blood and peripheral tissues. To accomplish this we will determine the role of these endothelial progenitors in maintaining the integrity of the vascular endothelium and the response of these progenitor cells to proangiogenic signals. Specifically we propose to: 1) Determine the endothelial cell potential of phenotypically defined subsets of normal adult bone marrow cells; 2) Evaluate the origin and functional activity of circulating endothelial progenitor cells and 3) Determine the capacity of bone marrow derived endothelial progenitor cells to enhance angiogenesis. These studies will identify bone marrow derived endothelial progenitors that in the future may be targeted to enhance vascular repair and to attenuate the progression of vascular disease.